We have identified a natural IgG antibody and a tumor associated IgM antibody with complement dependent cytotoxicity to certain tumor cells. These antibodies exist in whole sera bound in inactive form with antiidiotype antibodies. The targets for the former seem to be oncofetal antigens. We proposed to pursue these observations further. The effect of age upon serum titers of natural IgG antibody will be studied. We will seek the identity of antigens which react with serum IgM antibodies that are found in complex form with malignant myeloma. Sequential studies will be undertaken seeking a reciprocal relationship between IgG and IgM antibodies in patients with melanoma. The immunobiologic importance of these antibodies will be challenged in vivo using uncomplexed human antibodies and melanoma deposits in nude mice.